کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10583932 | 981312 | 2013 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Structural study of the location of the phenyl tail of benzene sulfonamides and the effect on human carbonic anhydrase inhibition
ترجمه فارسی عنوان
بررسی ساختاری محل سکون فنیل دم از بنزن سولفونامید ها و تأثیر آن بر مهار کربن انیدراتا انسانی
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کلمات کلیدی
کربن انیدراز، سولفونامید، بازدارنده کریستالوگرافی اشعه ایکس، دم، فنیل اتاتامیدو،
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
چکیده انگلیسی
The crystal structure of 4-phenylacetamidomethyl-benzenesulfonamide (4ITP) bound to human carbonic anhydrase (hCA, EC 4.2.1.1) II is reported. 4ITP is a medium potency hCA I and II inhibitor (KIs of 54-75Â nM), a strong mitochondrial CA VA/VB inhibitor (KIs of 8.3-8.6Â nM) and a weak transmembrane CA inhibitor (KIs of 136-212Â nM against hCA IX and XII). This elongated compound binds in an extended conformation to hCA II, with its tail lying towards the hydrophobic half of the active site whereas the sulfonamide moiety coordinates the zinc ion. The present structure was compared to that of structurally related aromatic sulfonamides, such as 4-phenylacetamido-benzene-sulfonamide (3OYS), 4-(2-mercaptophenylacetamido)-benzene-sulfonamide (2HD6) and 4-(3-nitrophenyl)-ureido-benzenesulfonamide (3N2P). Homology models of the hCA I, VA, VB, IX and XII structures were build which afforded an understanding of the amino acids involved in the binding of these compounds to these isoforms. The main conclusion of the study is that the orientation of the tail moiety and the presence of flexible linkers as well polar groups in it, strongly influence the potency and the selectivity of the sulfonamides for the inhibition of cytosolic, mitochondrial or transmembrane CA isoforms.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 21, 1 November 2013, Pages 6674-6680
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 21, 1 November 2013, Pages 6674-6680
نویسندگان
Ãzlen Güzel-Akdemir, Shyamasri Biswas, Katherine Lastra, Robert McKenna, Claudiu T. Supuran,